DESCRIPTION: The human genome is not a linear sequence, but rather a contorted knot of chromosomes in the three- dimensional space of the nucleus. Chromosomes do not work in isolation. Long-range interactions regulate gene expression. This innovation, however, has not been applied to viral infections. We still talk of host and pathogen genomes as if they are independent. I contend that these genomes are not separate, but rather an intertwined entity best referred to as a hosthogen genome. I propose to study long-range interactions between the human genome and latent Epstein-Barr virus (EBV). We will focus on connections mediated by the CCCTC-binding factor, a protein known to assemble interchromosomal loops. We have developed a method, the associated chromatin trap assay followed by deep sequencing (ACT-seq), to detect intergenome loops in a cell culture model of lymphoma. Persistent infection with EBV drives the development of cancer in AIDS survivors. This work may thus identify new drug targets that control viral genes responsible for HIV-associated malignancies.